London, UK – Researchers have found that children of women with HIV infection have an increased risk of immune abnormalities following exposure to maternal HIV viraemia, immune dysfunction, and co-infections during pregnancy.
The study, led by Dr Ceri Evans while at Queen Mary University of London, compared clinical outcomes between infants who were HIV-exposed and HIV-unexposed in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe. Despite high coverage of maternal antiretroviral therapy (ART) and uptake of exclusive breastfeeding, mortality in infants exposed to HIV was 41% higher than in infants not exposed to HIV. Infants who survived and remained HIV-free had impaired growth and development.
Analysis of blood samples from both mothers and children in the trial showed evidence of several biological pathways that contributed to the increased mortality seen in this cohort of infants. Systemic inflammation among women with HIV, as measured by C-reactive protein (CRP), was strongly associated with infant mortality, suggesting that interventions targeting maternal inflammation and its causes during pregnancy might reduce infant mortality. Researchers also found that the immune development of HIV-exposed babies – and especially boys – was different to those who had not been exposed to HIV, making it less effective in dealing with future infections. Infection with cytomegalovirus (CMV), which is a co-factor in HIV disease progression, was also found to be independently associated with infant mortality, as well as impacting on the development of the child’s immune system.
Dr Evans, NIHR Clinical Lecturer in Paediatric Infectious Diseases now at the University of Liverpool, said: ‘Collectively, these findings show how the skewed immune milieu of women with HIV in pregnancy – characterised by inflammation, immune dysfunction, and co-infections – shapes immune development in their offspring. Inflammation, as indicated by CRP, is inexpensive and simple to measure, offering the immediate opportunity for antenatal point-of-care testing to be used to identify those most at risk of infant mortality, with more support provided for high-risk pregnancies. CMV co-infection, which is common in sub-Saharan Africa, may offer a new intervention target to improve outcomes in this vulnerable population of children.’
Dr Marlène Bras, HIV Programmes and Advocacy Director at IAS – the International AIDS Society – said: ‘The IAS Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) awarded Dr Evans a grant in 2019 for his project, “The impact of improved water, sanitation and hygiene (WASH) on cytomegalovirus co-infection in HIV-affected mothers and children in rural Zimbabwe”. Dr Evans is a prime example of the importance of programmes such as CIPHER in supporting early-stage investigators and fostering innovative solutions for an integrated HIV response for infants, children, adolescents and young people living with and affected by HIV. We congratulate Dr Evans on his successes and look forward to working with him in the future.’
Paper details:
Ceri Evans et al. “Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants.” Published in Nature Communications.
DOI: 10.1038/s41467-023-44166-2
Available after publication at: https://www.nature.com/articles/s41467-023-44166-2
Funding information:
- Bill & Melinda Gates Foundation (OPP1021542 and OPP1143707)
- United Kingdom Department for International Development (DFID/UKAID)
- Wellcome Trust (203905/Z/16/Z (CE), 210807/Z/18/Z (CE), 093768/Z/10/Z (AJP), 108065/Z/15/Z (AJP), 206225/Z/17/Z (CDB; Wellcome Trust/Royal Society-funded Sir Henry Dale Postdoctoral Fellowship)
- CIPHER program of the International AIDS Society (grant number 2019/857-EVA) (CE)
- Swiss Agency for Development and Cooperation
- US National Institutes of Health (2R01HD060338-06)
- UNICEF (PCA-2017-0002)
Conflicts of Interest Disclosures: None
About Queen Mary
At Queen Mary University of London, we believe that a diversity of ideas helps us achieve the previously unthinkable.
Throughout our history, we’ve fostered social justice and improved lives through academic excellence. And we continue to live and breathe this spirit today, not because it’s simply ‘the right thing to do’ but for what it helps us achieve and the intellectual brilliance it delivers.
Our reformer heritage informs our conviction that great ideas can and should come from anywhere. It’s an approach that has brought results across the globe, from the communities of east London to the favelas of Rio de Janeiro.
We continue to embrace diversity of thought and opinion in everything we do, in the belief that when views collide, disciplines interact, and perspectives intersect, truly original thought takes form.
About the International AIDS Society
IAS – the International AIDS Society – convenes, educates and advocates for a world in which HIV no longer presents a threat to public health and individual well-being. After the emergence of HIV and AIDS, concerned scientists created the IAS to bring together experts from across the world and disciplines to promote a concerted HIV response. Today, the IAS and its members unite scientists, policy makers and activists to galvanize the scientific response, build global solidarity and enhance human dignity for all those living with and affected by HIV. The IAS also hosts the world’s most prestigious HIV conferences: the International AIDS Conference, the IAS Conference on HIV Science and the HIV Research for Prevention Conference.
About Wellcome
Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.
Contact
Honey Lucas
Queen Mary University of London
[email protected]